36 Yr. Old Has Repeated Implantation Failure With Great Embryos...What's Wrong?

Question:

Dear Dr,

We have just had our 4th failed IVF (in vitro fertilization).

Our history.  I am 36, my husband is 39. 1st pregnancy was in 2009 after 3 IuI's (intra uterine insemination) and clomid, but had to terminate at 15 weeks due to large enphaloceale (was a random genetic mutation)and my 2nd pregnancy with IUI was a success with a full term healthy baby boy.

Started with IuI's for 2nd child in 2011! We had 10 IuI's and now 4 IVF's.  Each IVF has been with icsi (intracytoplasmic sperm injection) and this time we had Embryo hatching. Last 3 transfers were 3 top grade 8 cell embryos each time on day 3.  I am not a great responder and only ever have 5-7 eggs, of which usually 4 fertilise.

I have had all the immunity checks done, my husbands sperm dna damage is within normal, fertilisation rate is good.  My ovarian reserve was also checked and the level was 1.0- My specialist said that he wasn't overly worried about the reserve for my age.  I have had a hysteroscopy and all normal.  I have been on various drug protocols and this last one was the long Lupron cycle with menapur.

We are just not sure what to do next?  Do we keep going, as my doctors are very positive and we have the finances. Are my doctors missing something?  Is there anything else we can do to improve our chances.  I am on DHEA and Royal Jelly, and my hubby is also on supplements.

I am writing from CapeTown, South Africa.

Thank you for your consideration, R.

Answer:

Hello R. from South Africa,

The exact cause of your failure cannot be known as there are still four steps your embryo has to go through in order to produce a pregnancy: embryo has to develop to blastocyst, the blastocyst has to hatch our of its shell, it then has to attach to the uterine lining and the lining has to grow around it.  As of now, there is no technology that can make this happen.  "Assisted hatching" is just making a defect in the shell so that the embryo can exit (hatch) more easily.

Something I always worry about when I have patients tell me they have failed multiple cycles despite good embryos, is the quality of the final step of the IVF process, which is the transfer.  You can have the absolute best and perfect embryos but if the transfer technique is not done well, then it will fail.  This has been shown by numerous studies.  Since you have been going to the same clinic, I wonder if that is not the problem, in which case, I would recommend that you seek out a different clinic.

One thing that I do with my patients that is not universally accepted but done by many of us, is to use a recurrent miscarriage protocol to reduce the immune system, thinking that a heightened immune system might be at fault.  For this regimen I add low dose heparin or lovenox, medrol, low dose aspirin, extra estrogen and extra progesterone (both injectable and vaginal).  I don't think that DHEA does anything so I don't use it.

At 36 years old, I have a 66% pregnancy rate in my clinic.  By two to three attempts with good 8 cell embryos, you should already be pregnant.  Your rate should especially be increased over other 36 year olds since you have been pregnant before.  For these reasons, I think the fault may lie in your clinic and not in you or your husband. 

Good luck in your journey to have a second child,

Edward J. Ramirez, M.D.
Executive Medical Director
The Fertility And Gynecology Center
Monterey Bay IVF
www.montereybayivf.com

 

Monterey, California, U.S.A.

Is A Big IVF Clinic Better Than A Small One?

Question:

Hello,

I am writing from Japan and want to ask that can big, crowded clinics be good or are small ones always good? Which is a worst choice...I'm very confused actually....like the crowded one has all the plus points, it is experienced, and cost is little bit lower than other. The big one has the pioneer in begining the IVF (in vitro fertilization) in Japan, the other has good success rates but only opened 6 yrs back...I'm totally confused!

How many cycles should a clinic do per year and what can I use to make my decision?

Please help ! H. from Tokyo

Answer:

Hello H. from Tokyo,

I run a smaller, low volume clinic and have better pregnancy rates that they large ones in my area, including the ones at Stanford University and the University of California, San Francisco.  I feel that I give better more personalized care because I am caring for them personally and completely.  I don't have other people doing what I should be doing.  The biggest disadvantage of a very large clinic is that it is a factory and depersonalized.  IVF should be a personal and intimate procedure, NOT a mechanical one.  So, of course I have a bias.  I would not recommend a small clinic that has a poor pregnancy rate, but if it has a good pregnancy rate, I think that is the better place to go.  I don't care how big and famous the larger clinic is or how many cycles they do, if it were me and my wife doing this I would want a clinic where the doctor is going to give us personalized attention the entire way, including personally do the retrieval and transfer procedures. I know that at the larger clinic in Japan you will rarely if EVER get to see the "famous" doctor,  so what good is it to go there? The smaller clinic will probably give you a better experience even though it is at a slightly higher cost.

In the U.S., people prefer to go to clinics where they get one on one personalized care, not where they are treated as another number.

幸運 ... Good Luck!

Edward J. Ramirez, M.D.
Executive Medical Director
The Fertility And Gynecology Center
Monterey Bay IVF
www.montereybayivf.com

Monterey, California, U.S.A.

 

How To Reduce The Risk Of OHSS

Question:

Hello,

I have been able to get pregnant naturally, but due to my kidney disease was not able to carry to term.  I have about 50 percent kidney function due to mild segmental mesangial sclerorsis.  I'm planning on pursuing surrogacy and would like to know what you would recommend for cycling treatment to reduce to the risk of OHSS (ovarian hyperstimulation syndrome) during the stimulation process?

Thank you, R. from California

Answer:

Hello R. from the U.S. (California),

First, I would choose a good IVF clinic.  OHSS is mostly due to overstimulation.  You'll want a doctor that is cautious, has a protocol to reduce the chances of developing OHSS and watches his patients carefully.

Second, OHSS tends to be most common in patients with PCOS where the ovaries are very sensitive to the stimulation.  If you don't have PCOS, then the chances of developing this problem are lower.

Third, patients at risk for OHSS get less medication than patients not at risk.  That is because their ovaries are so sensitive that they don't need much stimulation, and in fact, you don't want to stimulate them too strongly.  So a low dose FSH only or FSH/LH protocol is used.  I also don't use the "long protocol" in patients at risk for OHSS.  The long protocol is using Lupron injections starting from the luteal phase of the preceding cycle.  I use the antagonist protocol (the antagonist is to prevent spontaneous ovulation by suppressing the ovaries) which then allows me to trigger with Lupron instead of HCG (such as Ovidrel).

Finally, the estradiol levels and close monitoring of follicular growth are required so find a physician/clinic that works closely with their patients.  A large "factory" type of clinic is probably not a good choice. See this article regarding an American egg donor who underwent an IVF cycle through a Canadian clinic in 2011 to get an idea of the worst case scenario:  http://news.nationalpost.com/2013/03/28/kylee-gilman-sues-toronto-fertility-doctor/

Good Luck!

Edward J. Ramirez, M.D.
Executive Medical Director
The Fertility And Gynecology Center
Monterey Bay IVF
www.montereybayivf.com

Monterey, California, U.S.A.

National Infertility Awareness Week 2013....Join The Movement!

Dear Readers,
    This week, in the United States, through the great organization Resolve, we are promoting infertility awareness on many different venues...support groups, chats on Twitter and Facebook and over the blogosphere. April 21st - 27th, 2013 is National Infertility Awareness Week (NIAW).  NIAW is a week dedicated to bringing information about infertility to the public created by Resolve. Every year they have a theme. This year the theme is 'Join The Movement'. Although as an infertility physician blogger and a former infertility patient myself I joined the movement long ago, back in the mid-90's when my wife and I were going through IVF not many were aware or supportive of our journey. Fast forward to 2013 and it is amazing to see how much more aware the general public and the media are of the issues my patients face on a daily basis. It is due in large part to organizations like Resolve and the American Fertility Association and the many, many women bloggers and community forums that have joined ranks in spreading awareness. 

     There are many ways you can continue to spread awareness and inform yourself along the way. For starters there is the Resolve NIAW page where you can connect with some of the activities and teleconferences that will be going on this week. You can go online and keep apprized of the issues through spokeswoman Keiko Zoll's "The Infertility Voice" , where you can also get banners for your FB or Twitter pages. Resolve of New England is another excellent resource for information. This week they are featuring posts centered around IF such as, "From The First IVF Baby To Modern A.R.T." and "When To See A Fertility Specialist" all done by leading scientists and doctors in the field.

     Simple gestures such as following and posting #NIAW on Twitter and including your thoughts on infertility can spread the word as well. Another option is to follow infertility blogs like this one, "Where The *Bleep Is Our Stork", another simple way of showing your support for women like yourself who are going through IF.

     I close with the words of the above blogger regarding her feelings for this year's NIAW: "I don't want to be defined as "infertile", even if that is what I am. I want to be defined as inspirational and motivating and strong."  Kudos to her and to all of you for persevering and joining the movement!

32 Yr. Old Losing Hope After One IUI Miscarriage and One IVF Chemical Pregnancy: I Say Don't Give Up!!!

Hello, I don't even know how to begin because my infertility process has been so exhausting. I suppose I have diminished ovarian reserve. My last FSH check was 8.5. My AMH is 1. My stimulation cycles response seem to change--one time will be a nice response and the subsequent ones won't be. I started my first IVF this year and I fear repeating the same pattern as last year. Last year, my first IUI on 75 follistim/femara produced 4 mature eggs. I conceived, hcg was high, but ultimately a miscarriage due to trisomy 3. Did a complete RPL work up (I had a chemical pregnancy unmedicated 6 mos earlier). Nothing was abnormal, even karotyping. I had two more IUIs after that, producing 2 eggs, then only 1 egg. No success. I battled recurrent simple follicular cysts for about six months (would bounce from one ovary to next, two cyst aspirations and they would still come back) and finally had a cystectomy and laparoscopy in early February 2013. He found very mild endometriosis and treated it. I had started birth control pills in early January, on for 5 weeks, and then carried on with an antagonist protocol later in February with 150 follistim/75menopur. My day 4 E2 was over 700, thought I had another cyst, but instead had several follicles, dropped follistim to 75, then E2 dropped to 500, then up to 100 follistim and eventually my growth balanced out. Ultimately, I had 14 follices, 12 mature, 9 eggs retrieved, 6 fertilized, 4 day 3 embryos, then 2 highest grade blastocysts, 1 morula. Transferred the two blasts. Positive beta, 175 14 days after transfer. But my 48 hour beta dropped to 77. So I'm having another chemical pregnancy/miscarriage. This is exactly a year from my last miscarriage. I am terrified that in continuing IVF I will repeat this same pattern--that the next IVFs will not work. I just don't know what to do. I don't want to be 32 and have bad eggs when I know I don't have a translocation. I feel like I do respond to lower doses of medications, which should be indicative of decent reserve, but I don't know why I would keep having such problems likely due to embryo abnormalities. I suppose my uterus may have not been ready after the surgery and it wasn't the embryo but I took the good stuff-PIO, vivelle, dexamethasone, prednisone. Anyway, can these protocols be causing me an increased risk for aneuploid embryos? What could be changed? Any comforting words that I won't face the same fate with more IVFs that I did with the repeat IUIs? With it happening the same way all over again, I am believing I'll never have a baby. Last year was so hard, this IVF was hard. I’ve had to miss so much work, surgeries, U/S, procedures, etc. And I love my husband so much. I hate that I put him through this. Thank you, L. from Oklahoma Answer: Hello L. from the U.S. (Oklahoma), First let me clarify and emphasize to you that the IVF cycle worked, and you certainly have a good chance that it will continue to work in the future.  Your doctor probably did not explain that IVF only gives you the "chance" to get pregnant.  It, in fact, cannot MAKE you pregnant because the last three steps of the reproductive process are still beyond our technology to make happen.  These steps have to happen naturally (that part is still in God's hands).  So the fact that you got pregnant on your first IVF cycle is significant because it shows that you can get pregnant!  It is unfortunate, however, that it ended as a miscarriage. In terms of going through all of your previous pregnancies and this one, that would involve a more comprehensive analysis and explanation, that is beyond this venue.  I can do that by private consultation only. Second, I think you need to get the terms "decreased ovarian reserve" and "never" out of your vocabulary.  You DON'T have decreased ovarian reserve.  Keep in mind that in IUI cycles, we only want up to three mature sized follicles so that you don't get triplets, quadruplets, etc.  So, your responses were appropriate.  With your IVF cycle you were on a very low dose protocol and the yield was appropriate. . . not too strong and not too light.  You certainly could have been stimulated a little stronger, but it looks like your ovaries are very sensitive to the fertility medications so some care needs to be taken, as your doctor did. Finally, there is no technology that can predict or evaluate for internal embryo quality.  We can evaluate chromosomes so one option you certainly could consider with IVF is to have preimplantation genetic screening (PGS).  If you decide to do PGS, I would recommend a D#5 biopsy to reduce harm to the embryo, but your embryos would need to be frozen and transferred at a different cycle.  But that would allow you to evaluate the genetics of the embryo prior to transfer.  Your doctor would also need to stimulate a little stronger to have more embryos to work with and test since surely some will return abnormal.  This will then allow you to transfer normal embryos. All clinics, doctors and the protocols they use differ and that is what influences the pregnancy rates which vary from clinic to clinic.  There are other treatment protocol options; for example, I use low dose aspirin and low dose heparin in my recurrent pregnancy loss patients.  It has been well documented to help.  You might want to discuss that with your doctor. I want you to not lose hope.  You are young, your ovaries are still responsive and you've been pregnant, so now the goal is just to get a perfect embryo so that you can have the perfect baby.  Statistically, your chances are very very high, so you will eventually be successful.  You just need to hang in there and get the best treatment that you can.  Then once you have your baby, let me know so that I can celebrate your success as well.  You are on the road to success.  The only way you will surely fail, is if you deviate from than road.  Like Law school, this is a hard road, and it may not be fair, but in the end, it will be the most wonderful experience you've ever had in your life!  Greater than falling in love.  It was for me, and I thank God for his blessing that gave me my beautiful soon to be 16 year old IVF daughter.  Keep the faith in your path and in yourself.  Sorry for the long answer...good luck! Dr. Edward J. Ramirez, M.D., FACOG Executive Medical Director The Fertility and Gynecology Center Monterey Bay IVF Program www.montereybayivf.com

Woman Suspects She Has Endo: Treat The Pain Or Do IVF?

Question:

Hi there. Hubby and I have been TTC (trying to conceive) for almost 4 years now, with no success. We have been to two different REs, the first performed one HSG (hysterosalpingogram) and we underwent two unsuccessful IUIs (intrauterine insemination). The second ran a lot of tests, told me my eggs were low and wanted to go straight to IVF. In the last couple of years, my menstrual cramps have become unbearable, to the point of awaking me in the middle of the night. I have always had cramps, but nothing like this pain. I also have diarrhea along with my cycle, a yeast infection every month, and terrible seasonal allergies.

Two years ago I had an abdominal myomectomy and at that time, my doctor separated my fallopian tube from my uterus-they had gotten stuck together. I have been reading up on endometriosis and it sounds to me like I may have it. No doctor has ever suggested that I get tested for it. But I seem to have many symptoms of it. Do you think my tube and uterus getting stuck together were a result of undiagnosed endo? Could this be causing our infertility? Thank you for any answers you can provide. Thanks, W. From Virginia.


Answer: Hello W. from the U.S. (Virginia),

It seems that you are smarter than the two RE's that you consulted with. Given this history, you certainly could have endometriosis, and the prior surgery probably made the diagnosis. Endometriosis is one of the major causes of adhesions (scar tissue) formation in the pelvis. It can lead to infertility because it changes the normal anatomy and can prevent an egg from entering the tube. In addition, you have now had an open surgery (myomectomy) which is notorious for causing scar tissue formation as well. These two things on their own would explain your infertility.

At this point you have to make a decision: whether to treat the pelvic pain or get pregnant. Treating the pelvic pain will require additional surgery. Getting pregnant would require IVF, the only option for bypassing an abnormal pelvis. Do not be under the misunderstanding that doing the surgery to diagnose and treat the endometriosis and adhesions will restore your fertility. In fact, the opposite will occur because every surgery leads to further adhesion formation. Only do the surgery if the pain is a significant problem. If pregnancy is the priority, then go straight to IVF. In many cases, getting pregnant will help the endometriosis pain.

Good Luck,

Dr. Edward J. Ramirez, M.D., FACOG
Executive Medical Director
The Fertility and Gynecology Center
Monterey Bay IVF Program
www.montereybayivf.com

Young Woman With Endometriosis & PCOS Fails Five Clomid Cycles: Next Step?

Question:

Dear Doctor,

Hi, I'm from Minnesota. My husband and I have been trying to conceive since August of 2011. I have endometriosis and PCOS (polycystic ovarian syndrome) since finding out when I was around 17 years old, I'm 25 now. I have had five cycles of Clomid that didn't work. I had laparoscopy surgery for this post December, blocked tubes, suck ovaries, scar tissue, cysts and endometriosis. I'm on metformin because that's supposed to help with infertility and PCOS.

I started femara this month. Had 4 follicle on left and 1 on right from ultrasound. I usually ovulated on the 15th day, this time I didn't ovulate so I took the ovidrel shot and had a positive test. Started estrogen and progesterone day 3po. Currently on day 10po. I have cramps on and off.  I was just wondering what my chances of conceiving are and what is the next step if this didn't work this cycle. Any information or insight would be great! K. from Minnesota

Answer:

Hello K. from the U.S. (Minnesota),

Your statistical chances of pregnancy with Stage Four Endometriosis (endometriosis with extensive adhesive disease) and PCOD is probably less than 1% using any natural treatment method (Clomid, Femara or Injectables with intercourse or IUI).  That is because you have an abnormal pelvis and this location is critical for passage of the egg from the ovary to the tube.  Scar tissue, which is like spider webs, can block the egg from entering or reaching the tube.  Endometriosis causes a chronic inflammation of the pelvis which leads to the inflammatory cells attacking and destroying the egg as it exits the ovary to reach the tube. Polycystic ovarian disease is an ovarian dysfunction where the ovaries don't function properly and so there is a resultant hormone imbalance and lack of ovulation.  All of these put together significantly reduces your chances.

See my website for more extensive information and explanation of the options available for both Endometriosis and PCOS. I am convinced that with the proper information patients become empowered to make the right decision about their healthcare and can ascertain if they are receiving the best care.

It is my humble opinion that you are probably not seeing an infertility specialist because a good infertility subspecialist would have told you all this and not done all the treatments you have done.  The treatment of choice is to proceed to IVF so that you can bypass the pelvis completely.

Good Luck,

Dr. Edward J. Ramirez, M.D., FACOG

Executive Medical Director
The Fertility and Gynecology Center
Monterey Bay IVF Program
www.montereybayivf.com 

Monterey, California, U.S.A.